Project Summary Toxocara canis causes visceral and ocular larval migrans in humans. The reason why this disease cannot be eliminated is because tissue-dwelling larvae persist in the animal reservoir (dogs) where they tolerate anthelmintic treatment, and the mechanism for drug tolerance is unknown. Our hypothesis is that T. canis larvae evade drug treatment by effluxing antiparasitic drugs with permeability glycoproteins (P- glycoproteins) that efflux anthelmintics. In this application we propose to 1) record the repertoire of P- glycoprotein gene expression in T. canis, 2) map the precise tissues where P-glycoproteins are expressed, 3) demonstrate induction of P-glycoprotein activity by anthelmintic drugs, 4) characterize the unique pharmacology of T. canis P-glycoprotein, and 5) discover nematode-specific P-glycoprotein inhibitors that enhance the performance of antiparasitic drugs.